The long-term goal of this technology development project is to improve rehabilitation from lung disease through the development of the first truly portable, biocompatible, artificial lung capable of short and long term respiratory support. Current artificial lungs have recently been used to rehabilitate lung disease patients; however, significant advances in gas exchange, biocompatibility, and portability are required to fully realize their potential. Microfluidic artificial lungs promise to enable a new class of truly portable artificial lungs through feature sizes and blood channel designs that closely mimic those found in their natural counterpart. The objectives of the current R01 proposal, which seeks to propel our microfluidic artificial lung toward initial human applications, are to: 1) develop a roll-to-roll manufacturing system capable of producing the first human-scale microfluidic artificial lungs; 2) optimize the performance and biocompatibility of human-scale microfluidic artificial lungs; and, 3) test a human-scale microfluidic artificial lung in acute and chronic animal studies. These objectives are critical to advancing this promising technology toward initial acute systems for pulmonary rehabilitation.